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UMMC Guidance for Multisystem Inflammatory Syndrome in Children (MIS-C) Version 2

Note:  Guidance is based on expert consensus. Subspecialty consultation for individualized recommendations for suspected cases is strongly recommended.

Case Definition for Multisystem Inflammatory Syndrome in Children (MIS-C)*

  • A patient aged <21 years presenting with fever, laboratory evidence of inflammation, and evidence of clinically severe illness requiring hospitalization, with multisystem (>2) organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic or neurological); AND
  • No alternative plausible diagnoses; AND
  • Positive for recent SARS-CoV-2 infection by RT-PCR, serology, or antigen test; or COVID-19 exposure within 4 weeks prior to the onset of symptoms
  • Fever >38.0°C for ≥24 hours, or report of subjective fever lasting ≥24 hours
  • Evidence of inflammation: an elevated CRP, ESR, fibrinogen, procalcitonin, d-dimer, ferritin, lactic acid dehydrogenase (LDH), or interleukin 6 (IL-6), elevated neutrophils, reduced lymphocytes and low albumin
  • Some individuals may fulfill full or partial criteria for Kawasaki disease but should be reported (MSDH at 601 576 7725) if they meet the case definition for MIS-C
  • Consider MIS-C in any pediatric death with evidence of SARS-CoV-2 infection

* (


Figure 1. Diagnostic Pathway for MIS-C - PDF


  • All children admitted with concern for MIS-C: Peds ID, Peds Cardiology*, Peds Rheumatology, Peds Hematology
  • If with concern for thrombosis/HLH/MAS: Peds Heme/Onc and Peds Rheumatology
  • If with severe abdominal pain: Peds GI, Peds Surgery
  • If with neurologic findings: Peds Neurology
  • Additional consults based on presenting symptoms and clinical indications (Peds Nephrology, Peds Neurology, Dermatology)
    *Please note Pediatric Cardiology UMMC Guidelines for MISC posted also at this website


Therapeutic Categories:

  • Steroid Initial Dosing – the use of steroid should be discussed with Peds Rheumatology
  • Immunomodulators – the use of anakinra or other biologics for refractory illness course should be discussed with Peds Rheumatology and Peds Heme Onc
  • Anticoagulation – the use of LMWH or other anticoagulation regimen should be discussed with Peds Heme Onc
  • GI prophylaxis with PPI – while on steroid c/o primary team
  • Steroid taper – with subspecialty consultation Peds Rheumatology


  • All children meeting MIS-C criteria or with coronary ectasia should receive IVIG 2g/kg after subspecialty discussion
  • If 2-19 years of age should dose per IBW if actual body weight is > IBW by 20%. (and adults with BMI >30kg/m2)
  • Steroids should be considered also and discussed with PEDS Rheum and PEDS ID


  • Antibiotics: Ceftriaxone (alternative, ceftazidime) should be used as first-line empiric antibiotic coverage.
    • Add vancomycin if concerned for MRSA infection, including skin or soft tissue source, pneumonia, Gram positive bacteremia
    • Add metronidazole if concerned for intra-abdominal infection.
    • Use cefepime (alternative, meropenem) for patients who are immunocompromised, have a history of multi-drug resistant gram-negative bacterial infections, are critically ill, or if otherwise clinically indicated.
    • Consider further coverage for toxic shock syndrome or Rickettsia infection depending on patient presentation.
  • Anticoagulation: Please consult Heme/Onc to discuss. Please consider contraindications to anticoagulation (i.e., patients w/ PLT <30,000-80,000/uL, active bleeding, or significant bleeding risk). In general low dose ASA 3-5 mg/kg/day should be given until normalization of platelet count and confirmed normal coronaries at >/= 4 weeks after diagnosis. Enoxaparin should be considered also as prophylaxis/treatment (treatment dosing considered with coronary artery aneurysms with z score >/=10 or patients with documented thrombosis or an ejection fraction <35%).
  • Patients with GI Symptoms: These patients have higher risk of bowel perforation with pulse steroids. Consider risk/benefit of therapy in these patients.
  • Patients with Renal Injury: Consult Peds Nephrology and pediatric pharmacy for assistance in dosing medications.


Dermatologic: Take photo of rash/upload to Epic, Consider the following tests (HSV, VZV, enterovirus PCR); GI: Consider GI pathogen PCR panel; C difficile toxin PCR; Stool culture; Neurologic: Head imaging – consider if with focal neurologic deficit, altered mental status, seizure, severe headache with meningeal signs. If no contraindications, perform lumbar puncture (cell count, protein, glucose, culture, meningoencephalitis panel) AND CONSULT NEUROLOGY


PICUGeneral Pediatric Floor
  • Cardiac enzymes & BNP – every 48 hours (trend daily if abnormal)
  • 12L ECG every 1-2 days
  • ECHO – timing– discuss with Peds Cardiology
  • Cardiac enzymes & BNP – weekly (trend daily if abnormal)
  • 12L ECG every 2 days
  • ECHO –discuss with Peds Cardiology
  • Discuss with Peds Rheumatology regarding daily labs (CBC diff, CMP, ferritin, fibrinogen, D-dimer, triglycerides) for patients concerning for cytokine storm
  • Clinical change or abnormal trends/other labs warrant further evaluation to be determined by primary team


  • Steroid taper plan should be determined and clarified with Pediatric Rheumatology.
  • Ensure that plan for discharge ASA and enoxaparin are clear with Cardiology and Hematology and the parent. (e.g., if patient needs ASA if it is not given as an RX (tell the parents they have to get it separately).
  • Consider GI protective agent as many patients will be going home on ASA and steroid weans
  • All patients should have follow-up within 2 weeks post discharge with Pediatric Cardiology, Pediatric Infectious Disease (Dr C. Hobbs), Pediatric Rheumatology, and Pediatric Hematology (e mail Dr C. Gordon) for clinical evaluation, repeat echocardiogram. ALL APPOINTMENTS SHOULD BE MADE PRIOR TO DISCHARGE.
  • Exercise should be LIMITED until outpatient Cardiology appointment clears the child for resumption of activity
  • Live vaccines are not to be administered within 11 months of IVIG due to decreased potential efficacy.
  • Consider influenza shot (killed vaccine) if due, but ideally at least 1 month after cessation of steroids.

Contributors: Charlotte Hobbs, MD (Peds ID), Anita Dhanrajani, MD (Peds Rheumatology), Catherine Gordon, MD (Peds Heme Onc), Robert Santos, MD (Peds ID),  April Palmer, MD (Peds ID), Sue Phillips (Hospitalist), Linda Ray, MD, Charles Spencer, MD (Peds Rheumatology), Divya Shakti (Peds Cards), Jenny Hong (PICU).


Suggested readings and additional online resources for specialists caring for children with MIS-C:

American College of Rheumatology Clinical Guidance for Multisystem Inflammatory Syndrome in Children Associated With SARS–CoV‐2 and Hyperinflammation in Pediatric COVID‐19: Version 2. Arthritis Rheumatol.

The Children’s Hospital of Philadelphia (CHOP) clinical pathway for evaluation of possible MIS-C, Kawasaki pathway, suspected MIS-C with shock, and sepsis pathway:

Centers for Disease Control and Prevention. Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with Coronavirus Disease 2019 (COVID-19). Available at:

American Academy of Pediatrics, COVID-19 Interim Guidance: Return to Sports and Physical Activity. Available at: